Inside Health

Hepatitis C, a Silent Killer, Meets Its Match

Published: November 4, 2013

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To be sure, many of the new drug combinations have not been extensively tested yet. Side effects might still show up. And the drugs are not expected to work as well for patients with severe cirrhosis or those co-infected with H.I.V.

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Tom Espinosa, of Oakland, Calif., is eagerly awaiting the new hepatitis C drugs. He has advanced cirrhosis and spots on his liver that might be cancer.

“I just don’t think we know the answer until we get more widespread clinical experience,” said Charles M. Rice, a hepatitis C expert at Rockefeller University. “We may be in for some surprises still.”

New Direction

Researchers and patients have been disappointed before, when the first two direct-acting antiviral pills, telaprevir and boceprevir, reached the market in 2011. The drugs, which inhibited the virus’s protease enzyme, still required interferon and ribavirin, but they raised the cure rate to about 70 percent.

There was a huge rush to treatment. But doctors now say that side effects were worse than expected, in part because the sickest patients had been excluded from the clinical trials of the drugs.

“A lot of that didn’t come to light until after the drugs were approved,” said Dr. Brian R. Edlin, an associate professor of public health and medicine at Weill Cornell Medical College. “Then it turns out they were just horrible.”

Among the new drugs, the one garnering the most excitement is sofosbuvir, from Gilead Sciences, which is expected to be approved by the Food and Drug Administration by Dec. 8. It inhibits the virus’s polymerase enzyme, which builds new genomes out of RNA so the virus can replicate.

Sofosbuvir is an evil decoy of sorts. It looks like a building block of RNA. But once it is mistakenly incorporated into the RNA chain, the chain cannot grow and the virus cannot reproduce.

The effectiveness of the new drugs can vary depending on which strain of hepatitis C, known as genotypes, the patient has.

People infected with hepatitis C genotypes 2 and 3 — which account for 20 to 25 percent of cases in the United States — will take sofosbuvir with ribavirin but without interferon, making this the first all-oral treatment for hepatitis C. Treatment for genotype 2 will be 12 weeks, but for genotype 3 it will probably be 24 weeks.

Genotype 1, which accounts for more than 70 percent of patients in the United States, will still require interferon and ribavirin along with sofosbuvir, but only for 12 weeks. In a clinical trial, about 90 percent of previously untreated patients taking this combination achieved a sustained virologic response. The combination is expected to be somewhat less effective in those for whom previous treatments did not work.

Gilead hopes to have an all-oral treatment for genotype 1 approved by the end of 2014. It would be a once-a-day pill containing both sofosbuvir and another experimental Gilead drug, ledipasvir. This combination, used along with ribavirin, is what cured Dr. Rubens.

Other companies, including AbbVie, Merck and Bristol-Myers Squibb, are in a heated race to also bring all-oral combinations to market in the next two years or so.

Liver specialists will be able to put together an all-oral regimen for genotype 1 very soon, however, by prescribing both sofosbuvir and simeprevir, a Johnson & Johnson protease inhibitor that is expected to win approval soon. One study has shown this combination to be extremely effective, though insurers may balk at paying for two expensive drugs.

Awaiting Better Options

These new drugs are likely to alter the calculus about who gets treated and when.

Many doctors are now “warehousing” their hepatitis C patients — urging them to forgo treatment until the new drugs are approved.

“There’s no way I’m going to put them on an interferon regimen when we’re a year away from having interferon-free regimens,” said Dr. Scott Friedman, the chief of liver diseases at the Icahn School of Medicine at Mount Sinai. “It’s rare you have to pull the trigger and get them on treatment in that period of time.”

Gilead estimates that only 58,000 Americans with hepatitis C are now undergoing treatment, a small fraction even of those who know they are infected. Wanting to avoid interferon’s side effects, some patients without symptoms try to monitor their liver and start treatment only if it shows signs of deterioration.

But with the new more tolerable treatments, some experts say, it makes sense to treat early-stage disease to prevent cirrhosis and the accompanying risk of liver cancer.

And it is likely that more pre-symptomatic patients will be found through wider screening. Both the United States Preventive Services Task Force and the C.D.C. have recently begun to recommend that all baby boomers — people born from 1946 to 1964 — be tested for infection with hepatitis C, since they represent about three quarters of all cases.

“It will be test and treat,” said Dr. Eugene Schiff, the director of the liver diseases center at the University of Miami, who is a consultant to drug companies.

Pharmaceutical companies, of course, have a financial interest in seeing that more people get screened and treated, and they have been providing support for hepatitis C awareness campaigns and sponsoring studies on the benefits of screening and treatment.

The all-oral regimens also may make it more feasible to treat the people who are most likely to spread the virus — intravenous drug users, the homeless and prison inmates, many of whom also have mental health problems.

“I can’t treat an unstable patient safely with interferon,” said Dr. Diana Sylvestre, who runs a clinic in Oakland, Calif. that treats illicit drug users and former users. “But I can sure as hell give them a few pills.”